Is there sufficient evidence for a causal association between antiretroviral therapy and diabetes in HIV‐infected patients? A meta‐analysis

Abstract

The association of antiretroviral therapy (ART) with diabetes is inconsistent and varies widely across primary epidemiological studies. A comprehensive and more precise estimate of this association is fundamental to establishing a plausible causal link between ART and diabetes. We identified epidemiological studies that compared mean fasting plasma glucose (FPG) concentrations and proportions of diabetes and metabolic syndrome between HIV-infected patients naïve and exposed to ART. Mean difference in FPG concentrations and odds ratios of diabetes and metabolic syndrome were pooled using random-effects meta-analyses. Data on 20 178 participants from 41 observational studies were included in the meta-analyses. Mean FPG concentrations (Pooled mean difference: 4.66 mg/dL; 95% confidence interval [CI], 2.52 to 6.80; 24 studies) and the odds of diabetes (Pooled odds ratios: 3.85; 95% CI, 2.93 to 5.07; 10 studies) and metabolic syndrome (Pooled odds ratios: 1.45; 95% CI, 1.03 to 2.03; 18 studies) were significantly higher among ART-exposed patients, compared to their naïve counterparts. ART was also associated with significant increases in FPG levels in studies with mean ART duration ≥18 months (Pooled mean difference: 4.97 mg/dL; 95% CI, 3.10 to 6.84; 14 studies), but not in studies with mean ART duration <18 months (Pooled mean difference: 4.40 mg/dL, 95% CI, -0.59 to 9.38; 7 studies). ART may potentially be the single most consistent determinant of diabetes in people living with HIV worldwide. However, given the preponderance of cross-sectional studies in the meta-analysis, the association between ART and diabetes cannot be interpreted as cause and effect.

Diabetes, mortality and glucose monitoring rates in the TREAT Asia HIV Observational Database Low Intensity Transfer (TAHOD‐LITE) study

“…Evidence shows that PLHIV receiving ART are at increased risk of diabetes. A meta‐analysis found that PLHIV on ART had almost 4‐fold increased odds of having diabetes and, moreover, those on ART for > 18 months had significantly higher fasting plasma glucose (FPG) . Some antiretroviral drugs in particular, specifically zidovudine (ZDV), stavudine (d4T), didanosine (ddI), indinavir (IDV) and lopinavir (LPV), are thought to contribute to increasing FPG levels .…”

The effect of HIV infection on glycaemia and renal function in type 2 diabetic patients

“…Thus, Brown et al [ 2 ] observed that the prevalence of diabetes was up to four fold higher in HIV-infected men exposed to HAART compared to HIV-negative men. A recent meta-analysis confirms the strong association between the use of anti-retroviral therapy (ART) and increased risk for diabetes [ 3 ]. Furthermore, HIV-infected individuals have been found to have higher rates of metabolic syndrome, dyslipidaemia and lipodystrophy when compared to subjects without HIV infection [ 4 ].…”

Diabetes mellitus and its associated risk factors in patients with human immunodeficiency virus on anti-retroviral therapy at referral hospitals of Northwest Ethiopia

“…In particular, the development of diabetes mellitus in people living with HIV has also been shown to be contributed by the use of certain specific medications that are component of combination HAART regimens [18]. A meta-analysis conducted including 41 studies revealed that the risk of diabetes mellitus in PLWHIV was about four times more as compared with treatmentnaïve individuals, and has concluded HAART to be the single most important predictor of diabetes mellitus in people living with HIV [19].…”